Bis(ethylmaltolato)oxidovanadium (IV) mitigates neuronal apoptosis resulted from amyloid-beta induced endoplasmic reticulum stress through activating peroxisome proliferator-activated receptor γ
Bis(ethylmaltolato)oxidovanadium (IV) mitigates neuronal apoptosis resulted from amyloid-beta induced endoplasmic reticulum stress through activating peroxisome proliferator-activated receptor γ
复制标题
双(乙基麦芽糖)氧化钒 (IV) 通过激活过氧化物酶体增殖物激活受体 γ 减轻淀粉样蛋白 β 诱导的内质网应激引起的神经元凋亡
DOI：
10.1016/j.jinorgbio.2020.111073
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发表时间：
2020-07-01
影响因子：
3.9
通讯作者：
Liu, Qiong
中科院分区：
文献类型：
--
作者：
He, Zhijun;Wang, Menghuan;Liu, Qiong
β-淀粉样蛋白（Aβ）过度产生引起的神经元凋亡是阿尔茨海默病（AD）最重要的病理特征之一。 Aβ超载引起的内质网（ER）应激在此过程中发挥着关键作用。双（乙基麦芽糖）氧化钒（IV）（BEOV）是一种钒化合物，被认为是过氧化物酶体增殖物激活受体γ（PPARγ）激动剂，据报道对内质网应激具有拮抗作用。在本研究中，我们测试了 BEOV 是否可以通过抑制 ER 应激来改善 Aβ 诱导的神经元凋亡。据观察，BEOV 治疗通过降低原代海马神经元中 ER 应激相关蛋白和凋亡相关蛋白，以剂量依赖性方式改善衣霉素诱导和/或 Aβ 诱导的 ER 应激和神经毒性。与体外结果一致，BEOV 还减少了转基因 AD 模型小鼠海马和皮质中的内质网应激并抑制神经元凋亡。此外，通过分别采用GW9662和PPARγ抑制剂salubrinal和过度磷酸化真核翻译起始因子2α，我们进一步证实BEOV通过激活PPARγ减轻Aβ诱导的原代海马神经元内质网应激和神经元凋亡。总而言之，这些结果提供了科学证据来支持 BEOV 通过激活 PPAR gamma 改善 A beta 诱导的 ER 应激和神经元凋亡的概念。
Neuronal apoptosis caused by amyloid-beta (A beta) overproduction is one of the most important pathological features in Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress induced by A beta overload plays a critical role in this process. Bis(ethylmaltolato)oxidovanadium (IV) (BEOV), a vanadium compound which had been regarded as peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, was reported to exert an antagonistic effect on ER stress. In this study, we tested whether BEOV could ameliorate the A beta-induced neuronal apoptosis by inhibiting ER stress. It was observed that BEOV treatment ameliorated both tunicamycin-induced and/or A beta-induced ER stress and neurotoxicity in a dose-dependent manner through downgrading ER stress-associated and apoptosis-associated proteins in primary hippocampal neurons. Consistent with in vitro results, BEOV also reduced ER stress and inhibited neuronal apoptosis in hippocampi and cortexes of transgenic AD model mice. Moreover, by adopting GW9662 and salubrinal, the inhibitor of PPAR gamma and hyperphosphorylated eukaryotic translation initiation factor 2 alpha, respectively, we further confirmed that BEOV alleviated A beta-induced ER stress and neuronal apoptosis in primary hippocampal neurons by activating PPAR gamma. Taken together, these results provided scientific evidences to support the concept that BEOV ameliorates A beta-induced ER stress and neuronal apoptosis through activating PPAR gamma.